Effects of Intranasal Insulin on Neuroimaging Markers and Cognition in Patients With Psychotic Disorders

Phase 2

Completed

Conditions: Bipolar I Disorder
Psychosis
Schizo Affective Disorder
Schizophrenia

Interventions: Drug: Intranasal Insulin

Registration Number: NCT03943537

Lead Sponsor: Mclean Hospital

Brief Summary: This clinical trial is a single center, single dose study of the acute effects of intranasal insulin on energy metabolism and cognitive function in patients with schizophrenia, schizoaffective and bipolar disorders, compared and healthy controls.

Detailed Description: Psychotic disorders are common and severe psychiatric disorders. Despite advances in understanding the pathophysiology of these disorders, more effective and tolerable treatments are still needed. Evidence suggests that energy metabolism is altered in psychotic disorders. The investigators recently developed non-invasive MRI-based techniques to quantify redox balance and ATP generation in the brain. Targeting insulin pathways in the brain may allow for modulating abnormalities in energy metabolism. The investigators seek to examine whether intranasal insulin can modulate energy metabolism and improve cognition in patients with psychotic disorders. The study will use magnetic resonance spectroscopy (MRS) technology to measure in vivo energy metabolism processes in the brain, before and after the administration of intranasal insulin. Investigators will also measure changes in cognition with the administration of intranasal insulin.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 87

Inclusion Criteria

Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnoses of schizophrenia, schizoaffective disorder or bipolar disorder with psychotic features OR
Healthy Controls (no history of DSM psychiatric diagnoses, nor history of the same in first-degree relatives)

Exclusion Criteria

Psychiatric hospitalization within the last 4 weeks
Unstable/active disease or potential contraindications, such as liver disease, kidney disease, uncontrolled hypertension, significant or unstable medical illness
Currently prescribed: antidiabetic agents, including oral antidiabetic medications and insulin, intranasal medication, steroids, weight loss agents
Pregnant or breast-feeding, not using an effective form of contraception for at least 3 months, and/or not abstinent for 1 month prior to enrollment
History of significant head injury
Contraindication to MRI scans (claustrophobia, cardiac pacemakers, metal clips and stents on blood vessels, artificial heart valves, artificial arms, hands, legs, etc., brain stimulator devices, implanted drug pumps, ear implants, eye implants or known metal fragments in eyes, exposure to shrapnel or metal filings, other metallic surgical hardware in vital areas, certain tattoos with metallic ink, certain transdermal patches, metal-containing IUDs).
Medical conditions preventing blood draws
History of electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS) within the last 3 months
BMI > 35 or body weight > 350 lbs or BMI <18
DSM diagnosis of substance use disorder in the past month
For Healthy Controls:
Taking medication other than birth control

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Intranasal Insulin (40 IU)	Intranasal Insulin	40 IU Novolin-R insulin will be administered one time using the ViaNase intranasal delivery device.

Primary Outcome Measures

Name	Time	Method
Changes in Brain Redox State	6 hours, pre- and post- 40 IU intranasal insulin	Changes in brain NAD+/NADH ratio as measured by in vivo 31P magnetic resonance spectroscopy
Changes in Brain ATP	6 hours, pre- and post- 40 IU intranasal insulin	Changes in ATP concentration as measured by in vivo 31P magnetic resonance spectroscopy
Changes in Brain PCr	6 hours, pre- and post- 40 IU intranasal insulin	Changes in Phosphocreatine (PCr) concentration as measured by in vivo 31P magnetic resonance spectroscopy
Changes in Brain CK	6 hours, pre- and post- 40 IU intranasal insulin	Changes in creatine kinase (CK) enzyme rate as measured by in vivo 31P magnetic resonance spectroscopy
Changes in STROOP Color-word Interference Score	6 hours, pre- and post- 40 IU intranasal insulin	Changes in STROOP assessment color-word condition interference score. This score is calculated as follows, with C being the number of items answered correctly in the color condition, W being the number answered correctly in the word condition, and CW being the number of items answered correctly in the color-word condition: CW - (C x W)/(C+W). Higher scores indicate better cognitive function.
Changes in BACS Digit Sequencing Score	6 hours, pre- and post- 40 IU intranasal insulin	Changes in BACS digit sequencing scores, ranging from 0 - 36. Higher scores indicate better cognitive function.
Changes in BACS Symbol Coding	6 hours, pre- and post- 40 IU intranasal insulin	Changes in BACS Symbol Coding test, with scores ranging from 0 - 110. Higher scores indicate better cognitive function.
Changes in BACS Verbal Fluency Scores	6 hours, pre- and post- 40 IU intranasal insulin	Changes in BACS verbal fluency subscale z-scores, measured by number of words generated over 60-second trials. A z-score of 0 indicates the population mean. Higher scores indicate better cognitive function.

Secondary Outcome Measures

Name	Time	Method
Changes in Brain pH.	6 hours, pre- and post- 40 IU intranasal insulin	Changes in pH as measured by in vivo 31P magnetic resonance spectroscopy
Changes in Brain Inorganic Phosphate Concentration.	6 hours, pre- and post- 40 IU intranasal insulin	Changes in inorganic phosphate (Pi) concentration as measured by in vivo 31P magnetic resonance spectroscopy
Change in Fasting Blood Glucose Levels.	6 hours, pre- and post- 40 IU intranasal insulin	Safety outcome.
Change in Fasting Blood Insulin Levels.	6 hours, pre- and post- 40 IU intranasal insulin	Safety outcome.
Change in Brain Glutamate Concentration	6 hours, pre- and post- 40 IU intranasal insulin	Changes in glutamate (Glu) concentration as measured by in vivo proton magnetic resonance spectroscopy
Changes in Brain Glutamine Concentration	6 hours, pre- and post- 40 IU intranasal insulin	Changes in glutamine (Gln) concentration as measured by in vivo proton magnetic resonance spectroscopy
Changes in Brain Glutathione Concentration	6 hours, pre- and post- 40 IU intranasal insulin	Changes in glutathione (GSH) concentration as measured by in vivo proton magnetic resonance spectroscopy